S
ince chemotherapy was first used to
treat cancer in the 1940s, tumours
have been tackled according to their
organ or tissue of origin. Drugs used
for breast-cancer therapy, for exam-
ple, might be different from those used for
lung or colorectal cancers.
In the past few years, however, clinicians
have begun to use a new approach. Cancer is
now being defined and treated in a more per-
sonalized and precise way — tumour genomes
are sequenced so that people receive drugs
matched to the genetic profile of their cancer
cells. In 2017, the US Food and Drug Adminis-
tration (FDA) approved the first tissue-agnostic
drug for cancer — a treatment effective against
tumours with a specific genetic alteration,
regardless of the cancer’s location. Two more
tissue-agnostic drugs followed, in 2018 and- “It’s changing all of oncology,” says Razelle
Kurzrock, an oncologist and director of the
Center for Personalized Cancer Therapy at the
University of California, San Diego.Making the link
But experts disagree on how far this approach
can be taken. “A super small percentage of peo-
ple actually have their treatment changed as
a result of a tissue-agnostic approval,” says
Vinay Prasad, a haematologist–oncologist
at the University of California, San Francisco.
Although the drugs might be beneficial to
some people with rare cancers, most cancers
are not identified by a single genetic change.
And even when researchers find molecular
abnormalities that are common to tumours
in multiple parts of the body, treatment might
still have to be adjusted to take into account
other differences between and in tissues.
In 2012, cancer geneticist Bert Vogelsteinwas visited in his laboratory at the Sidney
Kimmel Comprehensive Cancer Center at
Johns Hopkins University in Baltimore,
Maryland, by a colleague with a puzzling
observation. A drug that was producing dra-
matic responses in people with advanced
skin and lung cancers, but that seemed inef-
fective against other cancers, had unexpect-
edly worked in a woman treated for colorectal
cancer. The colleague wanted to know why. “A
light bulb went off,” says Vogelstein. Because
both skin and lung tumours are notable for
their extraordinarily large numbers of genetic
mutations, he surmised that the woman’s
colorectal tumour had a DNA mismatch
repair deficiency (MMR-D) — an inability to
fix damaged DNA that results in hundreds to
thousands of mutations in coding regions,
especially in repetitive DNA regions known
as microsatellites.S16 | Nature | Vol 585 | 24 September 2020Precision oncology
outlook
A hopeful revolution in cancer care
Tissue-agnostic drugs that target genetic features rather than tissues have begun
to reach some people with cancer. But these early successes might prove to be the
exceptions. By Julianna PhotopoulosANTOINE DORE©
2020
Springer
Nature
Limited.
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rights
reserved. ©
2020
Springer
Nature
Limited.
All
rights
reserved.